Antibiotics Less Effective Than Surgery for Appendicitis

From Medscape Medical News

Laurie Barclay, MD

May 10, 2011 — Treating acute appendicitis with amoxicillin plus clavulanic acid was not noninferior to emergency appendectomy, according to the results of an open-label, noninferiority, randomized controlled trial reported in the May 7 issue of The Lancet.

"Researchers have suggested that antibiotics could cure acute appendicitis," write Corinne Vons, MD, PhD, from Assistance Publique-Hôpitaux de Paris and Université Paris XI, France, and colleagues. "We assessed the efficacy of amoxicillin plus clavulanic acid by comparison with emergency appendicectomy for treatment of patients with uncomplicated acute appendicitis."

At 6 university hospitals in France, 243 patients aged 18 to 68 years with uncomplicated acute appendicitis diagnosed on computed tomography (CT) scan were enrolled and randomly assigned, using a computer-generated sequence, either to receive amoxicillin plus clavulanic acid (3 g/day) for 8 to 15 days (n = 123) or to emergency appendectomy (n = 120).
The main study outcome was development of postintervention peritonitis within 30 days of starting treatment. Noninferiority was defined beforehand as the upper limit of the 2-sided 95% confidence interval (CI) for the difference in rates being lower than 10 percentage points. Analyses were by intention-to-treat, as well as per protocol.

Because of early dropout before receiving treatment, 4 patients were excluded from the intention-to-treat analysis, leaving 120 patients in the antibiotic group and 119 in the appendectomy group. Compared with the appendectomy group, the antibiotic group had a significantly higher frequency of postintervention peritonitis within 30 days (8% vs 2%; treatment difference, 5.8; 95% CI, 0.3 - 12.1).

Despite preoperative CT scan evaluation, 21 (18%) of 119 patients in the appendectomy group were unexpectedly found at surgery to have complicated appendicitis with peritonitis. Appendectomy was performed during the first 30 days in 14 of 120 patients (12%; 95% CI, 7.1% - 18.6%) in the antibiotic group, and in 30 of 102 patients (29%; 95% CI, 21.4% - 38.9%) in this group between 1 month and 1 year. Acute appendicitis was present in 26 of these patients (recurrence rate, 26%; 95% CI, 18.0% - 34.7%).

"Amoxicillin plus clavulanic acid was not non-inferior to emergency appendicectomy for treatment of acute appendicitis," the study authors write. "Identification of predictive markers on CT scans might enable improved targeting of antibiotic treatment."

Limitations of this study include a short follow-up period and the lack of masking of participants, clinicians, and research assessors.

In an accompanying comment, Rodney J. Mason, MD, PhD, from the University of Southern California Keck School of Medicine in Los Angeles, notes that antibiotics may have failed in some cases because of development of resistance, and that a different antibiotic regimen could produce better results in those cases.

"This acceptable alternative strategy is analogous to the present standard of care for recurrent uncomplicated diverticulitis," Dr. Mason writes. "Hopefully [the investigators'] conclusion, once the biases have been considered, will not overshadow major advances that have been made in the past 15 years towards the conservative treatment of appendicitis.
The fact that two-thirds of patients can be spared an operation deserves more attention."

The French Ministry of Health, Programme Hospitalier de Recherche Clinique 2002, supported this study. The study authors and Dr. Mason have disclosed no relevant financial relationships.

Lancet. 2011;377:1545-1546, 1573-1579. Summary